Statement byAnthony S. Fauci, M.D.
Director, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services
onHomeland Security: The Federal and Regional Response
before theHouse Committee on Science Subcommittee on Environment, Technology and Standards

June 10, 2002

The September 11, 2001, attacks on the World Trade Center and Pentagon changed forever our collective thinking with regard to the Nation's vulnerability to terrorist attacks. Superimposed on the events of September 11 were the first recorded cases of anthrax in the United States to result from an intentional human act. In addition to the tragic human toll of the anthrax attacks, the fear and disruption that they engendered were extraordinary, as were the associated economic costs.

The threat of bioterrorism has been addressed for years in the research portfolios of civilian agencies such as the National Institutes of Health (NIH), the Centers for Disease Control and Prevention (CDC), the Food and Drug Administration (FDA), as well as by the Department of Defense (DoD). Indeed, research on emerging and re-emerging diseases in general, including pathogens that could be intentionally released into human populations, has accelerated in recent years. However, the anthrax attacks of 2001 revealed significant gaps in our overall preparedness against bioterrorism, giving a new sense of urgency to biodefense efforts. In addition, recent revelations of massive, covert bioweapons programs in the former Soviet Union (where tons of deadly agents were stockpiled) and elsewhere underscore the need to significantly and rapidly bolster our ability to protect our citizens from anthrax, smallpox and other potential bioterror threats.

BIODEFENSE AND HOMELAND SECURITY

Homeland defense is a multifaceted endeavor, of which biodefense is a critical component. Our nation's ability to detect and counter bioterrorism depends to a large degree on the information generated by biomedical research on pathogenic microbes and the host response to these microbes; much of this research is supported by the NIH. The role of NIH biodefense research is to develop the tools necessary to protect civilians from potential agents of bioterrorism; this effort complements the long and successful history of the DoD in developing interventions to protect our troops against biological warfare. The threat of a bioterrorist attack against civilians differs in several ways from biowarfare directed at military personnel. Civilian populations are more vulnerable to such attacks because of their diversity with regard to age and health status. Civilians, unlike military personnel, generally will not have received vaccines to prevent infections with microbes that may be used as bioweapons. Moreover, the range of pathogenic microbes that might be used in a bioterrorist attack on civilians is much broader than what might be effectively used against the military. As we learned in the anthrax incidents of 2001, a bioterror attack against civilians is likely to be sudden and unexpected, requiring rapid diagnostics and therapies. While the NIH and DoD have a long-standing history of fruitful collaboration, these agencies have somewhat unique roles to play in the biodefense effort. In this regard, we feel a special responsibility to the public, who look to the NIH as the backbone of civilian biodefense through its biomedical research programs.

You have heard from Dr. Zerhouni about the President's proposal for a Department of Homeland Security to unify much of the Federal government's efforts to develop and implement scientific and technological countermeasures to chemical, biological, radiological, and nuclear threats. The NIAID looks forward to working closely with the Administration as overall plans for this new department are implemented.

IMMEDIATE NIH RESPONSES TO BIOTERRORISM

Since the fall of 2001, the NIH has moved quickly to accelerate basic and clinical research related to the prevention, diagnosis and treatment of diseases caused by potential agents of bioterrorism. These efforts have focused on the "Category A" agents considered by CDC to be the worst bioterror threats. These agents include the viruses that cause smallpox and hemorrhagic fevers such as Ebola; the bacteria that cause anthrax, plague, and tularemia; and botulinum toxin, as well as the many other pathogens that could potentially be used by bioterrorists. Category A agents cause high death rates or serious illness, are relatively easy to spread, and could cause panic or require special steps for public health preparedness. In the weeks and months following the first anthrax case in Florida, the NIH:

Accelerated the development of a "new generation" bio-engineered anthrax vaccine based on a portion of the anthrax bacterium known as protective antigen;

Conducted a study to show that existing stocks of smallpox vaccine could be diluted at least 5-fold, providing an immediate "cushion" of vaccine protection in case of a smallpox attack;

Expanded the genomic sequencing of the anthrax bacterium to include analysis of more than 15 strains, allowing the so-called Ames strain and the strain found at the site of the initial anthrax cases in Florida to be compared. The sequencing of the Florida strain was funded by the National Science Foundation;

Accelerated screening of antiviral compounds for activity against smallpox and related viruses;

Announced two pivotal studies, one that explains how the toxins of the anthrax bacterium destroys cells, and a second that demonstrated novel approaches to blocking the toxins;

Accelerated development of a promising Ebola virus vaccine developed by researchers at the Dale and Better Bumpers Vaccine Research Center of the National Institute of Allergy and Infectious Diseases (NIAID); and

Launched seven new fiscal year 2002 initiatives to expedite biodefense research (see www.niaid.nih.gov/newsroom/releases/accelbio.htm)

The response from the scientific community to the FY 2002 biodefense initiatives has been extraordinary; almost 700 proposals have been received. The outpouring of interest from concerned academic and industrial scientists, many of them leaders in their fields, has been unprecedented.

For fiscal year 2003, the President has proposed a $1.75 billion budget in biodefense research funding for NIH, which will enable the NIAID and other NIH institutes to expand ongoing projects and establish new initiatives as part of a comprehensive and sustained biodefense research program. We recently announced new opportunities for biodefense and emerging infectious diseases research as well as training and career development opportunities. Soon, we plan to announce 18 more biodefense research initiatives that focus on the research priorities delineated below. Of particular note are the planned renovation and construction of biosafety level (BSL)-3 and BSL4 facilities and the proposed funding of regional Centers of Excellence for Biodefense and Emerging Diseases Research. The Centers of Excellence for Biodefense and Emerging Diseases will not only provide state-of-the-science research capacity, but also will link to CDC and state and local health departments to provide permanent, regional expertise on agents of bioterror and other emerging and re-emerging diseases.

THE NIH BIODEFENSE RESEARCH AGENDA

As the lead agency at NIH for infectious diseases and immunology research, NIAID has developed a Strategic Plan for Biodefense Research, as well as a detailed Biodefense Research Agenda for CDC Category A Agents, with short-, intermediate-, and long-term goals. These documents can be found on the NIAID WWW site at www.niaid.nih.gov/dmid/bioterrorism. As part of the strategic planning process for our biodefense research agenda, the NIAID brought together many of the Nation's top experts for a Blue Ribbon Panel on Bioterrorism and its Implications for Medical Research. The panel comprised researchers from academic medical centers, private industry as well representatives from government and civilian agencies and the military. Participants were selected for their scientific expertise on the infectious agents considered to be major bioterror threats and on the host responses to pathogenic microbes, as well as for their scientific leadership and broad research experience.

The Strategic Plan and Research Agenda stress two over-arching and complementary components: basic research into agents with bioterrorism potential and the specific and non-specific host defense mechanisms against those agents; and applied research with pre-determined milestones for the development of new or improved diagnostics, vaccines and therapies. We focus on research in six key areas:

Microbial Biology. Research into the basic biology and disease-causing mechanisms of pathogens underpins all our efforts to develop interventions against agents of bioterrorism. NIAID supports extensive research to better understand the factors that influence the virulence and invasiveness of pathogens, as well as those that determine antibiotic resistance. An important new tool in understanding any microbe is our ability to rapidly obtain microbial genome sequence information, including that of potential bioterror agents. Many such agents, including smallpox and related viruses, already have been sequenced. Others are in the process of being sequenced, including multiple strains of the anthrax bacterium Bacillus anthracis, as well as the bacteria that cause, plague, botulism, Q fever, brucellosis and glanders. Coupled with recent advances in biochemistry, microbiology, and immunology, genomic information contributes greatly to efforts to develop new or improved diagnostic tests, therapies and vaccines for major bioterror threats. In particular, comparative genomics (comparing the sequences of different strains of particular organisms) will be an important component of future research, helping us to understand what makes a particular organism either harmful or benign.

Host Response to Microbes. In order to develop safe and effective vaccines, accurate diagnostics, and immunotherapeutics against microbes that may be used as bioterrorist agents, research has been accelerated to improve our understanding of the complex parameters of two components of the human immune system: innate and adaptive immunity. Because most potential bioterror agents would infect via the respiratory or oral routes, special attention is being paid to studies of mucosal immunity at these sites.

Vaccines. NIAID has bolstered research efforts on vaccines against many of the infectious agents considered to be bioterrorist threats, with an eye toward producing products that are safe and effective in civilian populations of varying ages and health status. As noted above, a clinical trial at several NIAID Vaccine and Treatment Evaluation Units (VTEUs) has demonstrated that the existing U.S. supply of smallpox vaccine  15.4 million doses  could successfully be diluted at least five-fold and retain its potency, effectively expanding the number of individuals who could potentially be vaccinated against smallpox (see www.niaid.nih.gov/newsroom/releases/smallpox.htm). In addition, the ongoing production of a "second-generation" smallpox vaccine produced in cell culture will increase our supply to approximately 286 million doses by the end of 2002. Moreover, the U.S. Department of Health and Human Services recently announced that it will be receiving more than 75 million additional doses of smallpox vaccine that has been stored by a pharmaceutical company since 1972; this additional vaccine supply will be tested for safety and immunogenicity by NIAID. In the long-term, basic research promises to provide a third generation of smallpox vaccines that could be used in all segments of the population, including pregnant women and people with weakened immune systems. One such vaccine nearing phase I clinical trials is based on a virus called Modified vaccinia virus Ankara (MVA), which is related to the current smallpox vaccine strain, but may cause fewer adverse reactions.

Additional bioterrorism vaccines also are in development. As noted above, a new anthrax vaccine, based on a bioengineered component of the anthrax bacterium called recombinant protective antigen (rPA), will soon enter human trials. On the NIH campus, researchers at the NIAID Dale and Betty Bumpers Vaccine Research Center have developed a DNA vaccine that protected monkeys from infection with Ebola virus, and that will soon be tested in human volunteers.

Therapeutics. To provide the capability of treating victims of a bioterrorist attack, NIH supports the development and clinical testing of therapeutics for the diseases that result from such attacks. NIH research goals include identifying several drugs for each agent of bioterror; developing "broad-spectrum" medicines that are effective against multiple agents; and designing new drugs for known and potentially drug-resistant microbes. This research involves the development of new antimicrobials and antitoxins, as well as the screening of existing antimicrobial agents to determine whether they have activity against potential bioterror agents. For example, in collaboration with DoD and with support from CDC, NIAID has rigorously screened more than 500 antiviral drugs against smallpox-related viruses. One of these agents is an antiviral drug called cidofovir, which is approved by the Food and Drug Administration (FDA) for treating certain AIDS-related viral infections. Both intravenous and oral versions of cidofovir have shown potent activity against smallpox and/or related viruses in test tube studies and in animal models. NIAID has taken the lead in developing a protocol that would allow cidofovir to be used in emergency situations for the treatment of smallpox.

Concurrently, other potential anti-smallpox agents are being investigated, and several promising leads will be further tested. The recently established Orthopoxvirus Genomics and Bioinformatics Resource Center, a collaborative project of NIAID, the Defense Advanced Research Projects Agency (DARPA), CDC, the U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID) and the American Type Culture Collection, promises to accelerate the development of new treatments  as well as vaccines  by providing sequence and functional comparisons of viral genes that will yield targets for the design of antivirals and vaccines.

Together with the FDA, CDC, and DoD, NIH has accelerated testing of promising new anthrax therapies. As mentioned above, NIAID-supported investigators recently published two studies in the scientific journal Nature that help to explain how anthrax toxin destroys cells. In one study, researchers identified the site on the cell that binds the anthrax toxin and have developed a compound that may disable it. Another group of investigators has characterized the structure of a major component of the anthrax toxin. The information gained through these studies will likely hasten the development of new drugs to treat anthrax

Diagnostics. An unusual upturn in cases of a disease, or a disease outbreak, likely will be the first sign of a bioterrorist attack. It is critically important to rapidly identify the microbe in the people who have become ill or in the environment where they work and live. NIAID supports research to develop ways to identify natural and bioengineered microbes, and to quickly establish a microbe's sensitivity to drug therapy.

Research Resources. Basic research and the development of new vaccines, therapeutics, and diagnostics depend on the availability of specialized research resources, such as genomics/proteomics information, appropriate animal models, standardized reagents, and high-containment laboratory facilities. As noted above, NIH plans to establish regional Centers of Excellence for Biodefense and Emerging Diseases Research, develop centralized research reagent repositories, and expand the number of BSL-3 and BSL-4 facilities necessary to work with the most dangerous pathogens.

In addition to physical resources, NIAID will recruit and train the best and the brightest individuals at various levels to execute the research agenda.

SPIN-OFFS OF BIOTERRORIM RESEARCH FOR OTHER DISEASES

We anticipate that the large investment in biodefense research will have many positive "spin-offs," similar to the manner in which HIV/AIDS research has advanced the understanding and treatment of many other diseases. NIH research on microbial biology and on the pathogenesis of organisms with bioterror potential will almost certainly lead to an enhanced understanding of other more common and naturally occurring infectious diseases that afflict people here and abroad. In particular, the advancement of knowledge should have enormous positive impact on our ability to diagnose, treat and prevent major diseases such as malaria, tuberculosis, HIV/AIDS, and a spectrum of emerging and re-emerging diseases such as West Nile fever, dengue, influenza, and multi-drug resistant microbes. The NIH biodefense research program also will greatly enhance our understanding of the molecular and cellular mechanisms of the innate immune system and its relationship to the adaptive immune system. This clearly will help in the search for new ways to treat and prevent a variety of immune-mediated diseases such as systemic lupus erythematosus, rheumatoid arthritis and other autoimmune diseases. In addition, new insights into the mechanisms of regulation of the human immune system will have positive spinoffs for diseases such as cancer, immune-mediated neurological diseases, allergic and hypersensitivity diseases, as well as for the prevention of rejection transplanted organs.

CONCLUSION

In recent months, NIH has made substantial progress in the biodefense research effort; however, much remains to be accomplished. Our experience with HIV/AIDS and the many life-saving advances that have resulted from NIH-sponsored HIV/AIDS research provides a model or paradigm of what can be accomplished with proper commitment to biodefense research. Building on the investments the President has requested, we fully expect that our scientists will develop the tools of diagnosis, treatment and prevention that will allow us to respond effectively to, and likely deter, future bioterrorist attacks on our citizens.

ANTHONY S. FAUCI, M.D.
Director, National Institute of Allergy and Infectious Diseases
National Institutes of Health

Dr. Anthony S. Fauci, a native of Brooklyn, New York, received his M.D. degree from Cornell University Medical College in 1966. He then completed an internship and residency at The New York Hospital-Cornell Medical Center. In 1968, Dr. Fauci came to the National Institutes of Health (NIH) as a clinical associate in the Laboratory of Clinical Investigation (LCI) at the National Institute of Allergy and Infectious Diseases (NIAID). In 1974, he became Head of the Clinical Physiology Section, LCI, and in 1980 was appointed Chief of the Laboratory of Immunoregulation, a position he still holds. Dr. Fauci became Director of NIAID in 1984.

Dr. Fauci has made many contributions to basic and clinical research on the pathogenesis and treatment of immune-mediated diseases. He has pioneered the field of human immunoregulation by making a number of basic scientific observations that serve as the basis for current understanding of the regulation of the human immune response. In addition, Dr. Fauci is widely recognized for delineating the precise mechanisms whereby immunosuppressive agents modulate the human immune response. He has developed effective therapies for formerly fatal diseases such as polyarteritis nodosa, Wegener's granulomatosis, and lymphomatoid granulomatosis. A 1985 Stanford University Arthritis Center Survey of the American Rheumatism Association membership ranked the work of Dr. Fauci on the treatment of polyarteritis nodosa and Wegener's granulomatosis as one of the most important advances in patient management in rheumatology over the previous 20 years.

Dr. Fauci has made seminal contributions to the understanding of how the AIDS virus destroys the body's defenses leading to its susceptibility to deadly infections. He has also delineated the mechanisms of induction of HIV expression by endogenous cytokines. Furthermore, he has been instrumental in developing strategies for the therapy and immune reconstitution of patients with this serious disease, as well as for a vaccine to prevent HIV infection. He continues to devote much of his research time to identifying the nature of the immunopathogenic mechanisms of HIV infection and the scope of the body's immune responses to the AIDS retrovirus.

In 1995, an Institute for Scientific Information study indicated that in the period of 1981-1994, among more than 1 million scientists throughout the world who published during that time frame, Dr. Fauci was the fifth most cited. Through the years, Dr. Fauci has served as Visiting Professor at major medical centers throughout the country. He has delivered many major lectureships all over the world and is the recipient of numerous prestigious awards for his scientific accomplishments, including 22 honorary doctorate degrees from universities in the United States and abroad.

Dr. Fauci is a member of the National Academy of Sciences, the American Philosophical Society, the Institute of Medicine of the National Academy of Sciences (Council Member), the American Academy of Arts and Sciences, and the Royal Danish Academy of Science and Letters, as well as a number of other professional societies including the American College of Physicians, the American Society for Clinical Investigation, the Association of American Physicians, the Infectious Diseases Society of America, and the American Academy of Allergy Asthma and Immunology. He serves on the editorial boards of many scientific journals; as an editor of Harrison's Principles of Internal Medicine; and as author, coauthor, or editor of more than 1,000 scientific publications, including several textbooks.